Topological superfluidity with repulsive alkaline-earth atoms in optical lattices

Topological superfluids are of technological relevance since they are believed to host Majorana bound states, a powerful resource for quantum computation and memory. Here we propose to realize topological superfluidity with fermionic atoms in an optical lattice. We consider a situation where atoms in two internal states experience different lattice potentials: one species is localized and the other itinerant, and show how quantum fluctuations of the localized fermions give rise to an attraction and strong spin-orbit coupling in the itinerant band. At low temperature, these effects stabilize a topological superfluid of mobile atoms even if their bare interactions are repulsive. This emergent state can be engineered with ${}^{87}$Sr atoms in a superlattice with a dimerized unit cell. To probe its unique properties we describe protocols that use high spectral resolution and controllability of the Sr clock transition, such as momentum-resolved spectroscopy and supercurrent response to a synthetic (laser-induced) magnetic field

Glucose induced toxicity to cells: protective effects of momordica charantia

Increased advanced glycation endproducts (AGEs) formation and oxidative stress are believed to underlie the pathogenesis of diabetic vascular complications including the impairment of the wound healing. In most developing countries, diabetic treatment is expensive and plants provide a cheap potential natural source of anti-diabetic remedies. Several studies have examined the beneficial effects of using Momordica charantia (MC) because of its hypoglycaemic properties in diabetic subjects. Here, for the first time, the anti-glycation and antioxidant properties of aqueous extracts of Momordica charantia pulp (MCP), flesh (MCF) and charantin were assessed in vitro. Since wound-healing is one of the most costly complications and affecting 15% of diabetic patients, the potential angiogenic activities of MCP, MCF and charantin in the presence or absence of AGEs were investigated. Lysozyme was glycated using either glucose or methylglyoxal in the presence or absence of 5 to 15 mg/ml of Momordica charantia extracts in 0.1 M sodium phosphate buffer (pH 7.4) at 37°C for three days. The formation of glucose or methylglyoxal-derived AGE crosslinks was assessed using sodium dodecyl sulphate-polyacrylamide gel electrophoresis followed by Coomassie blue staining. A non-competitive ELISA method was used to investigate the effect of Momordica charantia extracts on carboxymethyllysine (CML) concentrations. Antioxidant activities of all extracts of Momordica charantia were evaluated using the stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl radical-scavenging activity, metal chelating activity and reducing power. The phenolic, flavonols and flavonoid contents of all extracts were also measured. In vitro angiogenic assays including cell proliferation, migration and endothelial tube formation in Matrigel™ were used to assess the potential angiogenic effects of the natural extracts. By Western blotting, the angiogenic signalling pathways induced by AGEs and potentially modulated by MCP, MCF and charantin were also investigated. Furthermore, the neutralization of the receptor for AGEs (RAGE) was performed using a monoclonal anti-RAGE antibody to highlight the role of RAGE in the modulation of AGE-induced signalling pathways followed addition of MCP, MCF and charantin. All extracts inhibited the formation of MG-derived AGEs in a dose-dependent manner and the MCF extract showed the most potent inhibitory effect on both AGE and CML formation. Antioxidant capacity of MCF was significantly higher than MCP based upon the DPPH and hydroxyl radical-scavenging activity (p < 0.005); however, MCP shows higher metal-chelating activity in comparison to other extracts. The content of phenolic compounds was expressed in gallic acid equivalents (GAE), whereas flavonols and flavonoid contents were expressed in rutin equivalents (RE). In addition, all Momordica charantia extracts increased bovine aortic endothelial cell (BAEC) proliferation, migration and tube formation with induction of p-ERK1/2 expression through RAGE. Moreover, these natural extracts decreased the anti-angiogenic effects of high concentration of BSA-AGEs. Momordica charantia does not only have established hypoglycaemic effects but this study shows that crude extracts are capable of preventing MG-derived cross-linked AGEs and Glyoxalic acid-derived CML at least in vitro. This anti-glycation activity might be due to their antioxidant properties from their phenolic content. Furthermore, because of its pro-angiogenic effects and its ability to reduce the AGEs-induced anti-angiogenic effect, Momordica charantia presents a promising natural product for the development of a new strategy to accelerate wound-healing especially in diabetic foot. Thus, use of Momordica charantia deserves more attention in particular its ability to reduce AGE formation and oxidative stress in diabetic subjects and as a pro-angiogenic therapy

Momordica charantia extracts protect against inhibition of endothelial angiogenesis by advanced glycation endproducts in vitro.

Diabetes mellitus characterized by hyperglycemia favors formation of advanced glycation endproducts (AGEs) capable of triggering vascular complications by interfering with imbalanced inflammation and angiogenesis to eventually impede wound-healing. Momordica charantia (MC, bitter melon) has been shown to prevent AGE formation and to promote angiogenesis in diabetic wounds in animal models. However, the mechanism underlying its effects on angiogenesis is unclear. We investigated the effects of methanolic extracts of MC pulp (MCP), flesh (MCF) and charantin (active component of MC) using an in vitro model of angiogenesis. MC extracts or low concentrations of bovine serum albumin-derived AGEs (BSA-AGEs) stimulated proliferation, migration (using wound-healing assay) and tube formation (using Matrigel™-embedded 3D culture) of bovine aortic endothelial cells (BAEC) together with increases in the phosphorylation of extracellular signal-regulated kinase (ERK)1/2, the key angiogenic signaling cytoplasmic protein. Blocking the receptor for AGEs (RAGE) inhibited low BSA-AGE- and MC extract-induced ERK1/2 phosphorylation and tube formation, indicating the crucial role of RAGE in the pro-angiogenic effects of MC extracts. Moreover, inhibitory effects of high BSA-AGE concentration on cell proliferation and migration were reduced by the addition of MC extracts, which reversed the BSA-AGE anti-angiogenic effect on tube formation. Thus, MC extracts exert direct pro-angiogenic signaling mediated via RAGE to overcome the anti-angiogenic effects of high BSA-AGEs, highlighting the biphasic RAGE-dependent mechanisms involved. This study enhances our understanding of the mechanisms underlying the pro-angiogenic effects of MC extracts in improvement of diabetes-impaired wound-healing

Antiglycation and antioxidant properties of Momordica charantia

The accumulation of advanced glycation endproducts (AGEs) and oxidative stress underlie the pathogenesis of diabetic complications. In many developing countries, diabetes treatment is unaffordable, and plants such as bitter gourd (or bitter melon; Momordica charantia) are used as traditional remedies because they exhibit hypoglycaemic properties. This study compared the antiglycation and antioxidant properties of aqueous extracts of M. charantia pulp (MCP), flesh (MCF) and charantin in vitro. Lysozyme was mixed with methylglyoxal and 0–15 mg/ml of M. charantia extracts in a pH 7.4 buffer and incubated at 37°C for 3 days. Crosslinked AGEs were assessed using gel electrophoresis, and the carboxymethyllysine (CML) content was analyzed by enzyme-linked immunosorbent assays. The antioxidant activities of the extracts were evaluated using assays to assess DPPH (1,1-diphenyl-2-picryl-hydrazyl) and hydroxyl radical scavenging activities, metal-chelating activity and reducing power of the extracts. The phenolic, flavonol and flavonoid content of the extracts were also determined. All extracts inhibited the formation of crosslinked AGEs and CML in a dose-dependent manner, with MCF being the most potent. The antioxidant activity of MCF was higher than that of MCP, but MCP showed the highest metal-chelating activity. MCF had the highest phenolic and flavonoid contents, whereas MCP had the highest flavonol content. M. charantia has hypoglycaemic effects, but this study shows that M. charantia extracts are also capable of preventing AGE formation in vitro. This activity may be due to the antioxidant properties, particularly the total phenolic content of the extracts. Thus, the use of M. charantia deserves more attention, as it may not only reduce hyperglycaemia but also protect against the build-up of tissue AGEs and reduce oxidative stress in patients with diabetes

Characterization of interaction sites between Kir6.0 and SUR subunits of ATP-sensitive potassium (Katp) channels

This study investigated cytoplasmic inter-subunit interactions between the Kir6.2 and SUR2A subunits of the cardiac ATP-sensitive potassium channel. The channels are a heterooligomeric complex of pore-forming Kir6.2 subunits and sulphonylurea receptor (SUR2A) subunits. Interactions between the cytoplasmic loops, the nucleotide binding domains (NBF1 and NBF2) of SUR2A and the full length of Kir6.2 were determined. In co-immunoprecipitation experiments, fragments from the C-terminal of SUR2A containing residues 1294-1358 tagged with Maltose-binding protein (MBP) showed binding with the full length Kir6.2 subunit, while residues between 1358-1545 did not. This indicated involvement of a 65 amino acid domain in the proximal C-terminal of SUR2A in forming a direct interaction with Kir6.2. When HEK 293 cells stably expressing Kir6.2/SUR2A channels were transiently transfected with SUR2A fragments containing residues 1294-1359, KATP current was decreased. This current reduction was due to a decreased number of channel subunits in the cell membrane; this was demonstrated by using immunocytochemistry, which showed that anti-K ATP channel subunit-associated fluorescence was lower in the cell membrane and increased in the intracellular compartment in the presence of the binding region.;Use of SUR2A/MRP1 chimaeras of the putative binding domain showed that the last eleven amino acids of the binding region were important for binding activity but that they do not contain all the elements necessary for binding. Co-immunoprecipitation and assays of disruption of functional channels with the binding domain chimaeras suggested an important role for the residues between 1318 and 1337 in the Kir6.2 binding motif within the SUR2A C-terminal domain

The consumption of 12 Eggs per week for 1 year does not alter fasting serum markers of cardiovascular disease in older adults with early macular degeneration

Some studies suggest that eating more than one egg daily may increase risk of death from cardiovascular disease. The objective of this study was to determine the effects of consuming eggs on various serum markers associated with cardiovascular disease (CVD). Forty-five independently living adults diagnosed with early macular degeneration, but healthy otherwise were recruited into the study. Subjects were placed into the Intervention (n = 27) or Control group (n = 18) based on whether or not they would consume eggs. The Intervention group consumed 12 eggs per week while the Control group refrained from consuming any whole egg products for 1 year. Serum concentrations of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), glucose, apolipoprotein (apo) A-1 and apo B, lipoprotein (Lp)a and high-sensitive C reactive protein (hsCRP) were measured at baseline, 6, and 12 months. Serum low-density lipoprotein cholesterol (LDL-C) concentration was calculated via the Friedewald equation. Serum TC, TG, HDL-C, LDL-C, apo A-1, apo B, Lpa and hsCRP concentrations did not change at any time in both the Intervention and Control groups compared to baseline nor were there any differences between the two treatment. Serum glucose concentrations did increase significantly in the Intervention group at 6 months compared to baseline (23%, P < 0.05) but decreased back to baseline concentrations at 12 months. This study suggests that the consumption of 12 eggs per week for 1 year does not significantly alter fasting serum lipids, lipoprotein cholesterol, or other biomarkers of CVD in older adults diagnosed with early macular degeneration. Keywords: Apolipoprotein A-1, Apolipoprotein B, C-reactive protein (CRP), Cardiovascular disease (CVD), HDL cholesterol, LDL cholestero

ISVASE: identification of sequence variant associated with splicing event using RNA-seq data

Abstract Background Exon recognition and splicing precisely and efficiently by spliceosome is the key to generate mature mRNAs. About one third or a half of disease-related mutations affect RNA splicing. Software PVAAS has been developed to identify variants associated with aberrant splicing by directly using RNA-seq data. However, it bases on the assumption that annotated splicing site is normal splicing, which is not true in fact. Results We develop the ISVASE, a tool for specifically identifying sequence variants associated with splicing events (SVASE) by using RNA-seq data. Comparing with PVAAS, our tool has several advantages, such as multi-pass stringent rule-dependent filters and statistical filters, only using split-reads, independent sequence variant identification in each part of splicing (junction), sequence variant detection for both of known and novel splicing event, additional exon-exon junction shift event detection if known splicing events provided, splicing signal evaluation, known DNA mutation and/or RNA editing data supported, higher precision and consistency, and short running time. Using a realistic RNA-seq dataset, we performed a case study to illustrate the functionality and effectiveness of our method. Moreover, the output of SVASEs can be used for downstream analysis such as splicing regulatory element study and sequence variant functional analysis. Conclusions ISVASE is useful for researchers interested in sequence variants (DNA mutation and/or RNA editing) associated with splicing events. The package is freely available at https://sourceforge.net/projects/isvase/

Readmissions and Emergency Department Visits after Bariatric Surgery at Saudi Arabian Hospital: The Rates, Reasons, and Risk Factors

Background: Saudi Arabian hospital readmissions and emergency department (ED) visits following bariatric surgery and discharge have never been investigated. This study aimed to evaluate the rates and reasons of hospital readmissions and ED visits related to surgical weight loss interventions at the King Abdulaziz Medical City - Riyadh. Methods: We conducted a retrospective cohort study on 301 patients who underwent bariatric surgery between January 2011 and July 2016. We reviewed patient medical records progressively to assess hospital readmission, ED visits, and complications. Results: Of the 301 patients analyzed, 67.1% were female and 93% had class II obesity. The readmission rate, ED visit rate after discharge and the rate of either of the two was 8%, 14%,and 18.3%, respectively. The most common causes of readmission were abdominal pain (37.5%), nausea/vomiting (29.2%), and site leak (25%), while the most common causes of ED visits were abdominal pain (59.5%) and nausea/vomiting (16.9%). Readmission rates tended to be higher in older patients (age of patients readmitted 42 ± 12.1 years vs. age of patients not readmitted 34.3 ± 11.8 years; p = 0.002). The rate of readmission tends to increase in patients with overweight or class I obesity (odds ratio (OR) = 20.15), diabetes (OR = 14.82), and obstructive sleep apnea (OR = 14.29). Dyslipidemia was positively associated with ED visits (p = 0.027, OR = 2.87). The rate of readmission or ED visits increased with age, while there were decreases in readmission and ED visits for those who had received gastric sleeve surgery. Conclusions: The study reported high rates of readmission and ED visits, thus the effectiveness of different types of weight loss surgeries should be further evaluated, particularly in individuals with complicated medical issues such as diabetes, dyslipidemia, and obstructive sleep apnea